Radiation induced xerostomia is a common side-effect when treating head and neck cancer during and after therapy (Mira J G, Fullerton G D, Wescott W B. Correlation between initial salivary flow rate and radiation dose in the production of xerostomia. Acta Radiol Oncol. 1982;21:151-4, Jellema A P, Doornaert P, Slotman B J, Leemans C R, Langendijk J A. Does radiation dose to the salivary glands and oral cavity predict patient-rated xerostomia and sticky saliva in head and neck cancer patients treated with curative radiotherapy? Radiother Oncol. 2005;77:164-71, Porter S R, Fedele S, Habbab K M. Xerostomia in head and neck malignancy. Oral Oncol. 2010;46:460-3). Xerostomia is the subjective feeling of oral dryness, whereas hyposalivation is the physiological reduction in salivary flow (Nieuw Amerongen A V, Veerman E C. Current therapies for xerostomia and salivary gland hypofunction associated with cancer therapies. Support Care Cancer. 2003;11:226-31). Hyposalivation is defined as unstimulated whole saliva flow of ≤0.2 mL/min. Very low saliva flow below 0.1 mL/min is part of the criteria for diagnosing Sjögren's syndrome. Symptoms of xerostomia become evident when saliva flow is about 0.1-0.2 mL/min (Wolff M, Kleinberg I. Oral mucosal wetness in hypo- and normosalivators. Arch Oral Biol. 1998;43:455-62, Flink H, Tegelberg A, Lagerlof F. Influence of the time of measurement of unstimulated human whole saliva on the diagnosis of hyposalivation. Arch Oral Biol. 2005;50:553-9). In healthy individuals, 0.5-1.5 L of saliva is produced daily. Saliva is secreted by the three paired major salivary glands and consists of approximately 99% water and 1% proteins and salt (Navazesh M, Kumar S K. Measuring salivary flow: challenges and opportunities. J Am Dent Assoc. 2008;139 Supp1:35s-40s). Normal daily secretion of saliva is vital for maintaining good oral health, nutrition intake and communication skills (Navazesh M, Kumar S K. Measuring salivary flow: challenges and opportunities. J Am Dent Assoc. 2008;139 Suppl:35s-40s).
The occurrence of radiation induced xerostomia can be illustrated with data from the Danish Head and Neck Cancer Group's database (DAHANCA). From January 2000 to December 2012, 1238 head and neck cancer patients from Odense University Hospital were scored by an observer-based system regarding xerostomia. The higher the score, the more profound the symptoms of xerostomia were. FIG. 1 illustrates how 45% of all patients coming to their first follow-up visit two to five months after finishing radiation therapy suffered from a slight degree of xerostomia (score 1). Thirty-one percent suffered from severe xerostomia (score 2 and 3). All DAHANCA xerostomia scores were rated by the treating physician.
Xerostomia is not necessarily associated with a significant reduction in salivary flow, but can merely be defined according to the symptoms presented by patient. To assess the severity of xerostomia in the clinic, a good approach is to make use of an observer-based system (e.g. the DAHANCA follow-up scoring system) along with a validated QOL measurement device (e.g. the EORTC H&N35 questionnaire) and salivary measurement (Deasy J O, Moiseenko V, Marks L, Chao K S, Nam J, Eisbruch A. Radiotherapy dose-volume effects on salivary gland function. Int J Radiat Oncol Biol Phys. 2010;76:S58-63).
Radiation causes a deficiency in saliva production and thickens the composition of saliva due to irradiation of the saliva glands. Radiotherapy may result in eating difficulties and unintended weight loss, dysphagia, dysgeusia, difficulties speaking, disturbed sleep, and general oral discomfort (Dost F, Farah C S. Stimulating the discussion on saliva substitutes: a clinical perspective. Aust Dent J. 2013;58:11-7, Furness S, Bryan G, McMillan R, Birchenough S, Worthington Helen V. Interventions for the management of dry mouth: non-pharmacological interventions. Cochrane Database of Systematic Reviews [Internet]. 2013; (9). Available:http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD009603.pub3/abstract, Jensen A B, Hansen O, Jorgensen K, Bastholt L. Influence of late side-effects upon daily life after radiotherapy for laryngeal and pharyngeal cancer. Acta Oncol. 1994;33:487-91). The severity of xerostomia is affected by the total dose of radiation and is often irreversible (Jensen A B, Hansen O, Jorgensen K, Bastholt L. Influence of late side-effects upon daily life after radiotherapy for laryngeal and pharyngeal cancer. Acta Oncol. 1994;33:487-91, Mortensen H R, Overgaard J, Specht L, Overgaard M, Johansen J, Evensen J F, et al. Prevalence and peak incidence of acute and late normal tissue morbidity in the DAHANCA 6&7 randomised trial with accelerated radiotherapy for head and neck cancer. Radiother Oncol. 2012;103:69-75). Quality of life may become compromised and social activities limited. Various treatments are available to relieve the discomfort of xerostomia, including symptomatic relief by oral lubricants and saliva substitutes. Salivary stimulants may be considered where residual salivary gland function remains (Dirix P, Nuyts S, Vander Poorten V, Delaere P, Van den Bogaert W. The influence of xerostomia after radiotherapy on quality of life: results of a questionnaire in head and neck cancer. Support Care Cancer. 2008;16:171-9).
Object and Summary of the Invention
It is an object of the present invention to provide a chewing gum composition for use in the alleviation of xerostomia induced by radiotherapy treatment, the chewing gum composition comprises gum base and substantially no flavour ingredients.
It has surprisingly been found that it is possible to relieve the discomfort of xerostomia in patients that have been subjected to radiotherapy treatment. The flow of saliva is increased and the composition of the saliva becomes less thick after using the chewing gum composition according to the present invention.
Moreover, the invention also relates to a dosage regimen for administering the chewing gum composition for use in alleviation of xerostomia induced by radiotherapy treatment. So in one embodiment of the invention the chewing gum composition is administered to a human subject before and/or during and/or after radiotherapy treatment.